We propose to work in three areas of somatic cell genetics: gene localization and related phenomena, control mechanisms, and chemical mutagenesis. The production of human X human cell hybrids in culture will be studied, and attempts made to force a reductive (tetrapolar) division in these cells, to define linkage groups and examine the possibility of mitotic crossing-over. Evidence for reactivation of the inactive X chromosome upon hybridization will be sought with selective markers. Folate reductase will be purified from our mutant hamster cells with markedly increased reductase activity, to determine if the latter is due to overproduction. Finally mutagenesis of mouse, hamster and human cells will be studied with various agents, in order to obtain new markers for gene localization, study reverse mutation and constitutive mutants if possible, and develop practical screening systems for potential human mutagens.